The objective of this proposal is to uncover the mechanism(s) by which human cytomegalovirus (CMV) activates cellular DNA synthesis, and to ascertain whether an interdependence exists between the functions involved in the stimulation of cell DNA synthesis and the transforming potential of this virus. We will first define the conditions of interactions between the virus and the host cells which result in a massive induction of cellular DNA synthesis. To this end, temperature-sensitive mutants as well as populations of defective CMV particles which induce cellular DNA synthesis, will be isolated. The viral functions responsible for the stimulation of cellular DNA synthesis will then be characterized. The interactions between the genome of the infecting virions and that of cells stimulated to synthesize cellular DNA will be studied and the expression of viral functions in "immortalized" cells will be ascertained.